Association Between ECG Abnormalities and Fatal Cardiovascular Disease Among Patients With and Without Severe Mental Illness

BACKGROUND: ECG abnormalities are associated with adverse outcomes in the general population, but their prognostic significance in severe mental illness (SMI) remains unexplored. We investigated associations between no, minor, and major ECG abnormalities and fatal cardiovascular disease (CVD) among patients with SMI compared with controls without mental illness. METHODS AND RESULTS: We cross‐linked data from Danish nationwide registries and included primary care patients with digital ECGs from 2001 to 2015. Patients had SMI if they were diagnosed with schizophrenia, bipolar disorder, or severe depression before ECG recording. Controls were required to be without any prior mental illness or psychotropic medication use. Fatal CVD was assessed using hazard ratios (HRs) with 95% CIs and standardized 10‐year absolute risks. Of 346 552 patients, 10 028 had SMI (3%; median age, 54 years; male, 45%), and 336 524 were controls (97%; median age, 56 years; male, 48%). We observed an interaction between SMI and ECG abnormalities on fatal CVD (P<0.001). Severe mental illness was associated with fatal CVD across no (HR, 2.17; 95% CI, 1.95–2.43), minor (HR, 1.90; 95% CI, 1.49–2.42), and major (HR, 1.40; 95% CI, 1.26–1.55) ECG abnormalities compared with controls. Across age‐ and sex‐specific subgroups, SMI patients with ECG abnormalities but no CVD at baseline had highest standardized 10‐year absolute risks of fatal CVD. CONCLUSIONS: ECG abnormalities conferred a poorer prognosis among patients with SMI compared with controls without mental illness. SMI patients with ECG abnormalities but no CVD represent a high‐risk population that may benefit from greater surveillance and risk management.